Human Circulating Plasmablasts Are Not Blasting: A Probable Misnomer

Abstract

Abstract Following infection or vaccination, antibody-secreting cells (ASC), also called plasmablasts, appear in circulation transiently; a small fraction of them then migrate to the spleen or bone marrow (BM) to mature into long-lived plasma cells (LLPC). While LLPC, by definition, are quiescent or non-dividing, early-minted blood ASC were mostly thought to be “blasting” or proliferative. In this study, we show <3% of LLPC are Ki-67+ with none taking up BrdU. In contrast, nearly all (>95%) nascent blood ASC express Ki-67 but only 10–15% actually incorporate BrdU. Due to the limitations of traditional flow cytometry, we integrated an optofluidic technology capable of single-cell visualization into a unique ASC survival system to directly evaluate both cell division status and ongoing antibody secretion. In agreement with the literature, LLPC displayed no proliferative potential. Surprisingly, only 11–13% of the blood ASC displaying ongoing antibody secretion had divided by day 10–14. Thus, while newly-generated ASC in the blood have recently undergone proliferation, the majority have exited the mitotic cell cycle and are not actively “blasting”. As they further mature into terminal LLPC, they undergo complete cell cycle arrest. Therefore, the term “plasmablast” may actually be a misnomer. Supported by NIH/NIAID 1R01AI121252, 1P01AI125180, U01AI141993, U54CA260563, U19AI110483, T32AI070081 and the Bill & Melinda Gates Foundation Grant INV-002351.